1. Technical Field of the Invention
The invention relates to, as novel and useful industrial products, a novel class of biaromatic compounds which are activators of receptors of Peroxisome Proliferator-Activated Receptor type of sub-type γ (PPAR-γ). The invention also relates to a process for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions.
2. Description of the Prior Art
The activity of receptors of PPAR type has been the subject of many studies. Mention may be made, as a guide, of the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes during the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol 111, 1998, pp. 1116-1121, in which is listed a large number of bibliographic references relating to receptors of PPAR type. Mention may also be made, as a guide, of the report entitled “The PPARs: From orphan receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, pp. 527-550.
PPAR receptors activate transcription by binding to elements of DNA sequences, known as peroxisome proliferator response elements (PPRE), in the form of a heterodimer with retinoid X receptors (known as RXRs).
Three sub-types of human PPAR have been identified and described: PPARα, PPARγ and PPAR δ (or NUC1).
PPARα is mainly expressed in the liver, while PPARδ is ubiquitous.
PPARγ is the most extensively studied of the three sub-types. All the references suggest a critical role of PPARs γ in regulating the differentiation of adipocytes, where it is greatly expressed. It also has a key role in systemic lipid homeostasis.
It has been described in particular in patent application WO 96/33724 that PPARγ-selective compounds, such as a prostaglandin-J2 or -D2, are potential active agents for treating obesity and diabetes.
Moreover, the Applicant has already described in patent application FR98/02894 the use of PPARγ activator compounds in the preparation of a pharmaceutical composition, the composition being intended to treat skin disorders associated with an anomaly of epidermal cell differentiation.